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VAI Voice

The Official Blog of Van Andel Institute
13 Sep 2017

Investigating inherited Parkinson’s, gene by gene

For the majority of people with Parkinson’s disease, the cause of their condition is far from clear.

But for a small number, its genesis can be directly linked to genetic causes that are traceable through generations of their family history. Although people in this group comprise less than 10 percent of all cases, they harbor important clues that may one day be used to develop life-changing treatments for patients across the spectrum of Parkinson’s disease.

“Purely genetic cases of Parkinson’s are important to study on their own but at the same time, they give us insight into cases whose origin is less clear,” said Dr. Darren Moore, an associate professor in Van Andel Research Institute’s Center for Neurodegenerative Science. “Although no two cases of Parkinson’s are the same—including those caused by similar genetic changes—there are important common threads that offer hope for new therapies.”

Moore heads up a growing research program that investigates how changes in some of the Parkinson’s-related genes identified to date contribute to the disease’s onset. Among these are LRRK2, the most common cause of genetic Parkinson’s disease, and VPS35, a recently identified culprit in neurodegeneration.

Although these two genes have little to no overlap in function, they both play important, individual roles in cellular trash removal, an important process that keeps cells healthy and working properly.

Scientists are still investigating the specifics, but it’s thought that Parkinson’s may result when cells are unable to get rid of abnormal molecules or debris, which eventually causes inflammation and damages the cell. Once about 70 percent of these critical brain cells are damaged or dead, trademark symptoms of Parkinson’s, such as tremor and difficulty walking, begin to appear.

One of the biggest goals in Parkinson’s research is slowing or stopping this cell death, something no current therapy is able to do. By investigating known genetic causes of the disease, Moore and his team hope to deliver life-changing breakthroughs to the seven to 10 million people globally with the disease, both inherited and non-inherited.

To support their efforts, Moore recently was awarded a five-year, $2 million federal grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. Three postdoctoral fellows in his lab, early career scientists who are on the road to leading their own research programs, also recently received funding to support this work: Dr. Xi Chen was awarded $110,000 from the Parkinson’s Foundation, and Drs. An Phu Tran Nguyen and Sharif Islam were each awarded $35,000 from the American Parkinson Disease Association.

“There are some promising drugs in development that target LRRK2 but none that target VPS35,” he said. “We have a real opportunity in both cases to strengthen the rationale for doing so.”

Learn more about the Moore Laboratory and its work here.

Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number R01NS105432. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Xi Chen is supported by Parkinson’s Foundation and Drs. An Phu Tran Nguyen and Sharif Islam are supported by the American Parkinson Disease Association.